Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage
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Purpose
This large randomized trial tested whether phenobarbital given to a pregnant woman about to deliver a premature infant would prevent brain injuries in their newborns. Women with 24 to 32 week fetuses who were in preterm labor and were expected to deliver within 24 hrs were randomized to phenobarbital or usual care. They were treated until they deliver or the fetus reaches 33 wks gestation. Babies were followed until discharge and evaluated at 18-22 mos corrected age for neurodevelopmental outcome.
| Condition | Intervention | Phase |
|---|---|---|
|
Infant, Newborn Infant, Low Birth Weight Infant, Small for Gestational Age Infant, Premature Intracranial Hemorrhages |
Drug: Phenobarbital Drug: Saline |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Prevention |
| Official Title: | Randomized Clinical Trial of Antenatal Phenobarbital in the Prevention of Neonatal Intracranial Hemorrhage |
- Neonatal intracranial hemorrhage or death [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]
- Intracranial hemorrhage (grade I, II, III, or IV) [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]
- Periventricular leukomalacia [ Time Frame: 72 hours of life ] [ Designated as safety issue: Yes ]
- Neurodevelopmental impairment [ Time Frame: 18 to 22 months of corrected age ] [ Designated as safety issue: Yes ]
| Enrollment: | 610 |
| Study Start Date: | February 1993 |
| Study Completion Date: | February 1997 |
| Primary Completion Date: | February 1995 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Phenobarbital |
Drug: Phenobarbital
10 mg of phenobarbital per kilogram of body weight intravenously over a period of 20 to 40 minutes (maximal dose, 1000 mg)
|
| Placebo Comparator: Placebo |
Drug: Saline
Infusion of normal sal
|
Detailed Description:
The administration of phenobarbital to pregnant women before delivery has been thought to decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this potential neuroprotective therapy further, we determined the effect of antenatal administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and early death. Women who were 24 to 33 weeks pregnant and who were expected to deliver their infants within 24 hours were randomly assigned to receive either intravenous phenobarbital (10 mg/kg body weight) or placebo, followed by maintenance doses until delivery or 34 wks gestation. Infants less than 34 wks at birth underwent serial cranial ultrasonography to detect the presence of intracranial hemorrhage. The sample size of 1038 pregnancies was based on an intracranial hemorrhage rate of 20 percent in the placebo and less than 12 percent in the phenobarbital group; 90 percent power; a 5 percent two-tailed type 1 error; and an 8 percent noncompliance rate. The twin with the highest grade of intracranial hemorrhage was included.
Degree of maternal sedation was evaluated after administration of study drug. Neonatal ultrasound exams were performed at 3-5 days, 10-14 days, and 38-42 wks postmenstrual age; neonatal medications were recorded during the first week of life; treatments, and outcomes were recorded through death, discharge, or 120 days, whichever occurred first. Neurodevelopmental outcome was evaluated at 18-22 months corrected age by certified examiners masked to treatment status.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Admission to a high risk perinatal unit or labor and delivery unit;
- 24 to 32 completed weeks gestation;
- Expected delivery within 24 hrs;
- Preterm labor or no labor with planned delivery for maternal-fetal indications;
Exclusion Criteria:
- Anticipated delivery within two hours
- Multiple congenital or chromosomal abnormalities in the fetus
- Multiple gestation with more than two fetuses
- Administration of phenobarbital during the pregnancy
- Administration of indomethacin within one week before admission
- Maternal platelet count of less than 100,000 per cubic millimeter
Contacts and Locations| United States, California | |
| Stanford University | |
| Palo Alto, California, United States, 94304 | |
| United States, Connecticut | |
| Yale University | |
| New Haven, Connecticut, United States, 06504 | |
| United States, District of Columbia | |
| George Washington University | |
| Washington, District of Columbia, United States, 20052 | |
| United States, Georgia | |
| Emory University | |
| Atlanta, Georgia, United States, 30303 | |
| United States, Indiana | |
| Indiana University | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Michigan | |
| Wayne State University | |
| Detroit, Michigan, United States, 48201 | |
| United States, New Mexico | |
| University of New Mexico | |
| Albuquerque, New Mexico, United States, 87131 | |
| United States, Ohio | |
| Cincinnati Children's Medical Center | |
| Cincinnati, Ohio, United States, 45267 | |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | |
| Cleveland, Ohio, United States, 44106 | |
| United States, Rhode Island | |
| Brown University, Women & Infants Hospital of Rhode Island | |
| Providence, Rhode Island, United States, 02905 | |
| United States, Tennessee | |
| University of Tennessee | |
| Memphis, Tennessee, United States, 38163 | |
| Study Director: | Seetha Shankaran, MD | Wayne State University |
| Principal Investigator: | Lu-Ann Papile, MD | University of New Mexico |
| Principal Investigator: | Richard A. Ehrenkranz, MD | Yale University |
| Principal Investigator: | Raymond Bain, PhD | George Washington University |
| Principal Investigator: | James A. Lemons, MD | Indiana University |
| Principal Investigator: | Sheldon B. Korones, MD | University of Tennessee at Memphis |
| Principal Investigator: | David K. Stevenson, MD | Stanford University |
| Principal Investigator: | Edward F. Donovan, MD | Cincinnati Children's Medical Center |
| Principal Investigator: | Barbara J. Stoll, MD | Emory University |
| Principal Investigator: | Avroy A. Fanaroff, MD | Case Western Reserve University |
| Principal Investigator: | William Oh, MD | Brown University, Women and Infants Hospital |
More Information
Additional Information:
Publications:
| Responsible Party: | Seetha Shankaran/ Lead Principal Investigator, Wayne State University |
| ClinicalTrials.gov Identifier: | NCT00009620 History of Changes |
| Other Study ID Numbers: | NICHD-NRN-0006, U10HD021385, U10HD027881, U10HD027871, U01HD019897, U10HD027856, U10HD021415, U10HD027880, U10HD027853, U10HD027851, U10HD021364, U10HD027904, M01RR000997, M01RR006022, M01RR000750, M01RR000070, M01RR008084 |
| Study First Received: | February 1, 2001 |
| Last Updated: | January 9, 2011 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
|
Periventricular leukomalacia NICHD Neonatal Research Network Extremely Low Birth Weight (ELBW) Prematurity Cerebral hemorrhage Phenobarbital |
Pregnancy Prenatal care Intraventricular hemorrhage Brain injury Brain hemorrhage |
Additional relevant MeSH terms:
|
Birth Weight Hemorrhage Intracranial Hemorrhages Body Weight Signs and Symptoms Pathologic Processes Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Phenobarbital |
Hypnotics and Sedatives Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action GABA Modulators GABA Agents Anticonvulsants |
ClinicalTrials.gov processed this record on May 16, 2013